Primoz Strojan

Contemporary management of sinonasal cancer

Sinonasal cancer is a relatively uncommon entity encountered by head and neck oncologists, rhinologists, and skull base surgeons. Recent innovations in surgical and nonsurgical therapeutic modalities raise the question of whether there has been any measurable improvement for treatment outcomes.

Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in tissue and serum of head and neck squamous cell carcinoma patients

The aim of this study was to determine urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) concentrations in tumour and adjacent normal tissue samples from 58 patients, and in serum samples from 40 of 58 patients with squamous cell carcinoma of the head and neck obtained at diagnosis and after completion of therapy. uPA and PAI-1 serum concentrations were also measured in 28 healthy volunteers who served as controls. Measurements were made using enzyme-linked immunosorbent assay (ELISA) techniques. For both uPA and PAI-1, significantly elevated concentrations were measured in tumour tissue as compared with normal tissue (uPA: 8.89 versus 0.41 ng/mg total protein (mgp), P < 0.0001; PAI-1: 23.9 versus 1.47 ng/mgp, P < 0.0001). A statistically significant difference in uPA concentrations was found between normal laryngeal and nonlaryngeal tissue (0.52 versus 0.3 ng/mgp, P = 0.008), and in PAI-1 concentrations between T1 + 2 and T3 + 4 stage of disease (17.32 versus 35.63 ng/mgp, P = 0.04). The uPA concentrations positively correlated with those of PAI-1 measured in both tumour (Rs = 0.62, P < 0.0001) and normal tissue (Rs = 0.30, P = 0.02). In serum samples, lower concentrations of PAI-1 were measured in the control group than in patients with cancer (412.0 versus 680.5 ng/ml serum (mls), P = 0.0006). The time of collection of the serum sample did not influence uPA and PAI-1 concentrations, and no association was observed between their concentrations and any clinical and histopathological prognostic factors tested. Our results indicate that both uPA and PAI-1 may play a specific role in the process of invasion and metastasis, and might also be of prognostic value in squamous cell carcinoma of the head and neck.

The role of systemic therapy in the management of sinonasal cancer: A critical review

PURPOSE Due to the rarity and the variety of histological types of sinonasal cancers, there is a paucity of data regarding strategy for their optimal treatment. Generally, outcomes of advanced and higher grade tumors remain unsatisfactory, despite the employment of sophisticated surgical approaches, technical advances in radiation techniques and the use of heavy ion particles. In this context, we critically evaluated the role of systemic therapy as part of a multidisciplinary approach to locally advanced disease. RESULTS Induction chemotherapy has shown encouraging activity and could have a role in the multimodal treatment of patients with advanced sinonasal tumors. For epithelial tumors, the most frequently employed chemotherapy is cisplatin, in combination with either 5-fluorouracil, taxane, ifosfamide, or vincristine. Only limited experiences with concurrent chemoradiation exist with sinonasal cancer. The role of systemic treatment for each histological type (intestinal-type adenocarcinoma, sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, sinonasal primary mucosal melanoma, sarcoma) is discussed. CONCLUSIONS The treatment of SNC requires a multimodal approach. Employment of systemic therapy for locally advanced disease could result in better outcomes, and optimize the therapeutic armamentarium. Further studies are needed to precisely define the role of systemic therapy and identify the optimal sequencing for its administration in relation to local therapies.

Coupling treatment planning with navigation system: a new technological approach in treatment of head and neck tumors by electrochemotherapy

BackgroundElectrochemotherapy provides highly effective local treatment for a variety of tumors. In deep-seated tumors of the head and neck, due to complex anatomy of the region or inability to cover the whole tumor with standard electrodes, the use of long single needle electrodes is mandatory. In such cases, a treatment plan provides the information on the optimal configuration of the electrodes to adequately cover the tumor with electric field, while the accurate placement of the electrodes in the surgical room in patients can remain a problem. Therefore, during electrochemotherapy of two head and neck lymph-node metastases of squamous cell carcinoma origin, a navigation system for placement of electrodes was used.Patient and methodsElectrochemotherapy of two lymph-node metastases of cutaneous squamous cell carcinoma, one in the left parotid gland and the other in the neck just behind the left mandibular angle, was performed using intravenous administration of bleomycin and long single needle electrodes. The tumors were treated according to the prepared treatment plan, and executed with the use of navigation system.ResultsCoupling of treatment plan with the navigation system aided to an accurate placement of the electrodes. The navigation system helped the surgeon to identify the exact location of the tumors, and helped with the positioning of the long needle electrodes during their insertion, according to treatment plan. Five electrodes were inserted for each metastasis, one centrally in the tumor and four in the periphery of the tumor. Five weeks after electrochemotherapy, computed tomography images demonstrated partial response of the first metastasis and complete response of the second one. Six weeks after electrochemotherapy, fine-needle aspiration biopsy specimen obtained from the treated lesions revealed necrosis and inflammatory cells, without any viable tumor cells.ConclusionWe describe a new technological approach for electrochemotherapy of deep-seated head and neck tumors, coupling of the treatment planning with navigation system for accurate placement of the single long needle electrodes into and around the tumors, according to the treatment plan. Evidence of its effectiveness on two lymph-node metastases of cutaneous squamous cell carcinoma origin in neck lymph is provided.

Electrochemotherapy in non-melanoma head and neck cancers: a retrospective analysis of the treated cases.

Electrochemotherapy increases the permeability of tumours to drugs by electric voltages applied locally. Its value in tumours of the head and neck is unknown. We retrospectively reviewed a 2-centre database, and found 39 patients with squamous cell carcinoma (SCC) of the oral cavity or oropharynx (n=12) or non-melanoma skin tumours (n=27) who had been treated with bleomycin electrochemotherapy with needle electrodes. A further 3 patients were given cisplatin electrochemotherapy (n=2), or bleomycin electrochemotherapy by plate electrodes (n=1). Local toxicity was mild. The complete response rate was 38% and was associated with whether the tumour was primary or recurrent (p<0.001), its size (p=0.02), and the route by which the drug was given (p=0.02). We did not study enough patients with basal cell carcinomas to say whether the response was significantly better or not (p=0.07). Skin tumours and SCC of the oral cavity or oropharynx showed comparable complete responses (41% and 33%, p=0.73) and local control (1-year local progression-free survival, 51% compared with 59%, p=0.89), particularly if they were small (p=0.001), primary (p=0.002), chemonaive (p=0.03). Patients treated with cisplatin were unresponsive. Electrochemotherapy with bleomycin is an effective option for skin tumours of the head and neck and is a feasible alternative in highly selected (small, primary, and not previously treated by chemotherapy) SCC of the oral cavity and oropharynx.

Indications for radiotherapy after neck dissection

Up‐front surgery and postoperative radiotherapy constitute a well‐recognized treatment concept for locally or regionally advanced squamous cell carcinoma of the head and neck. This “treatment package” is further intensified with the concomitant application of chemotherapy during irradiation when high‐risk features (ie, microscopically involved resection margins, extracapsular extension of the tumor from neck nodes, the presence of soft tissue deposits) are found on histopathologic examination of a resected specimen. With regard to neck disease, however, the demarcation line between low‐ and higher‐risk clinical situations, which would differ with respect to the need for postoperative radiotherapy, is not clear. In an attempt to define the low‐risk characteristics of disease in the neck that do not require adjuvant irradiation, we reviewed the available literature reports for any direct or indirect evidence on the value of postoperative radiotherapy in various clinical scenarios. The number of positive lymph nodes found in a dissected tissue specimen that should be used as a “cut‐off” point for introduction of postoperative radiotherapy was evaluated in the context of both primary tumor characteristics and type of neck dissection.

Impact of primary tumor volume on local control after definitive radiotherapy for head and neck cancer

The impact of primary tumor volume (pTV) on local control after definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) is unclear.

Lymph node metastasis in nasal vestibule cancer: A review

Squamous cell carcinoma of the nasal vestibule (SCCNV) is an uncommon malignancy. Our purpose is to define the incidence of simultaneous and delayed regional metastasis in SCCNV according to the available literature.

Efficiency of electrochemotherapy with reduced bleomycin dose in the treatment of nonmelanoma head and neck skin cancer: Preliminary results

In the present study, effectiveness of electrochemotherapy was compared in patients with nonmelanoma skin cancer (NMSC) of the head and neck using standard and reduced doses of bleomycin.

Prognostic value of some tumor markers in unresectable stage IV oropharyngeal carcinoma patients treated with concomitant radiochemotherapy

Abstract Background. The aim of the study was to investigate how the expression of tumor markers p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31 influenced the outcome of advanced inoperable oropharyngeal carcinoma patients, treated with concomitant radiochemotherapy. Patients and methods. The pretreatment biopsy specimens of 74 consecutive patients with inoperable stage IV oropharyngeal squamous cell carcinoma treated with concomitant radiochemotherapy were in retrospective study processed by immunochemistry for p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31. Disease-free survival (DFS) was assessed according to the expression of tumor markers. Results. Patients with a high expression of p21 (≥10%), p27 (>50%), Ki-67 (>50%), CD31 (>130 vessels/mm2) and low expression of p53 (<10%), cyclin D1 (<10%) and EGFR (<10%) (favorable levels - FL) had better DFS than patients with a low expression of p21 (<10%), p27 (≤50%), Ki-67 (≤50%), CD31 (<130 vessels/mm2) and high expression of p53 (≥10%), cyclin D1 (≥10%) and EGFR (≥10%) (unfavorable levels - UL). However, statistical significance in survival between FL and UL was achieved only for p27 and cyclin D1. DFS significantly decreased with an increasing number of markers with an unfavorable level per tumor (1–4 vs. 5–7) (78% vs. 32%, respectively; p = 0.004). The number of markers per tumor with UL of expression retained prognostic significance also in multivariate analysis. Conclusions. Statistical significance in survival between FL and UL emerged only for p27 and cyclin D1. The number of markers per tumor with UL of expression was an independent prognostic factor for an adverse outcome.